Cognitive impairment is a frequent manifestation of advanced HIV infection. The treatment response to antiretroviral medications is often brief and unsatisfactory. We conducted a randomized double-blind, placebo-controlled trial using a parallel group, 2x2 factorial design of deprenyl, a monoamine oxidase B inhibitor, (2.5 mg 3 times a week) and thioctic acid, an antioxidant, (600 mg every 12 hours) in 15 patients with HIV associated cognitive impairment. Informed, witnessed, signed consent was obtained from all participants or from the person with durable power of attorney. The double-blind, placebo-controlled phase of the study was 10 weeks. After this phase, patients were eligible to receive 10 weeks of open label drug. Evaluations included neurological and neuropsychological assessments, concurrent medications, concurrent AIDS-defining illnesses, adverse experiences, activities of daily living assessment, and routine safety labs. Deprenyl recipients showed improved performance on a test of verbal memory and 1 test of psychomotor speed, compared to patients not taking deprenyl. Thioctic acid recipients did not show neuropsychological testing improvement. Both deprenyl and thioctic acid were well tolerated with few adverse events. These results suggest that both drugs are well tolerated in patients with advanced HIV infection, but only deprenyl treated patients showed cognitive improvement. The trial was completed as of 1/10/96.